The prospect of reversing senescence and restoring the proliferative potential of cells has implications in many fields of endeavor. Many of the diseases of old age are associated with the loss of this potential. Moreover, the tragic disease, Progeria, which is often described in the literature as a premature aging syndrome based on appearance, is associated with the loss of proliferative potential of cells. Werner Syndrome and Hutchinson-Gilford Progeria Syndrome (HGPS) are two progeroid diseases. A major clinical difference between the two is that the onset of Hutchinson-Gilford Progeria Syndrome (sometimes called progeria of childhood) occurs within the first decade of life, whereas the first evidence of Werner Syndrome (sometimes called progeria of adulthood) appears only after puberty, with the full symptoms becoming manifest in individuals 20 to 30 years old.
More particularly, Hutchinson-Gilford Progeria Syndrome (HGPS) (also referred to as Hutchinson-Gilford Syndrome or Progeria) is a very rare progressive disorder of childhood characterized by features of premature aging (progeria), failure to thrive usually beginning in the first year of life resulting in short stature and low weight, deterioration of the layer of fat beneath the skin (subcutaneous adipose tissue), and characteristic craniofacial abnormalities, including frontal bossing, underdeveloped jaw (micrognathia), unusually prominent eyes and/or a small, “beak-like” nose. In addition, during the first year or two of life, scalp hair, eyebrows and eyelashes may become sparse, and veins of the scalp may become unusually prominent. Additional symptoms and physical findings may include joint stiffness, repeated nonhealing fractures, a progressive aged appearance of the skin, delays in tooth eruption (dentition) and/or malformation and crowding of the teeth. Individuals with the disorder typically have normal intelligence. In most cases, affected individuals experience premature, widespread thickening and loss of elasticity of artery walls (arteriosclerosis), often resulting in life-threatening complications such as heart attacks and strokes which are the usual causes of death.
HGPS is thought to be a genetic disorder, yet the mode of inheritance, molecular basis, and pathogenic mechanism all remain elusive. It has in the past been thought to be due to a sporadic autosomal dominant genetic mutation.
The identification of mutations associated with HGPS would be an incredible breakthrough in detection, diagnosis, and prognosis of this disease, and would open avenues for treatment and possibly prevention of HGPS and related or similar conditions, including more generally arteriosclerosis and aging.